Brad S. Kahl, MD
Ibrutinib (Imbruvica) has been approved by the FDA for patients with relapsed/refractory mantle cell lymphoma (MCL) since 2013, and long-term follow-up data for the BTK inhibitor continue to demonstrate its clinical activity.
Results of a pooled analysis presented at the 2017 ASH Annual Meeting showed that more than one-quarter of patients with relapsed/refractory MCL remained progression free and nearly half were alive at 3 years when treated with ibrutinib.
The analysis included data from 370 patients enrolled across the PCYC-1104 (n = 111), SPARK (n = 120), and RAY (n = 139) studies. The median duration of follow-up was 41.1 months and the median treatment exposure was 11.1 months.
Complete responses were achieved by 26.5% of patients. At 2 and 3 years, 36% and 26% of patients were progression free, respectively. The median progression-free survival (PFS) was 13.0 months overall, 33.6 months in patients with 1 line of prior therapy, and 46.2 months in patients who achieved a complete response. Overall, 53%, 45%, and 37% of patients were alive at 2, 3, and 5 years, respectively. The median overall survival was 26.7 months.
“The data for ibrutinib are better than anything else in the second-line setting. That is the reason why it is becoming a commonly utilized second-line therapy in MCL,” said Brad S. Kahl, MD.
In an interview with OncLive,
Kahl, a professor in the Department of Medicine, Washington University School of Medicine in St. Louis, Siteman Cancer Center, discussed the latest data for ibrutinib and highlighted emerging treatments in MCL.
OncLive: Please discuss the evolving treatment options for patients with MCL.
Historically, there were not great options for relapsed/refractory MCL. We had conventional chemotherapy, which worked unsatisfactorily. We had bortezomib (Velcade), which had a relatively low overall response rate and short duration of response. We have had lenalidomide (Revlimid), which has a low response rate but can have durable responses for patients with relapsed MCL. When we were finally introduced to BTK inhibition, first with ibrutinib, we were happy to see higher response rates in the 60% to 70% range, along with better durability, with responses lasting an average of 18 months.
There were long-term follow-up data presented at the 2017 ASH Annual Meeting for ibrutinib from 3 studies that were pooled. It showed that for patients who have a complete response on ibrutinib, the median duration of response is over 4 years. That is much better than anything we have seen historically. That was a nice advance for recurrent MCL.
We were very happy to see acalabrutinib [Calquence] added into the mix a few months ago. The acalabrutinib data look similar and comparable to the ibrutinib data. When you compare the profiles of the 2 drugs, there is the suggestion that acalabrutinib might be better tolerated than ibrutinib. There is also a suggestion that acalabrutinib might have a better complete response rate than ibrutinib. They have not been compared in a head-to-head trial so we do not know for sure whether acalabrutinib offers significant advantages over ibrutinib. However, for those of us who treat these patients, we are happy to have acalabrutinib as an option. I suspect many physicians will be using that agent to get more experience with it.
Is the MCL treatment paradigm moving away from chemotherapy or will that still have a role?
Chemotherapy is still the mainstay for frontline treatment. None of the targeted therapies have moved their way firmly into frontline treatment. There are some important trials that should read out in the next year looking at adding BTK inhibition to chemotherapy. It is not like the chemotherapy was jettisoned; they are just looking at adding BTK inhibition to chemotherapy. For the foreseeable future, chemotherapy is going to be the mainstay of frontline therapy. There will be trials developed in the next few years that will challenge that paradigm, but those will not read out for a while. I see chemotherapy as the mainstay.